March 2019

Pharmaceutical focusExamining prophylactic intracameral antibiotics

In a recent study, investigators looked at intracameral injections of cefuroxime, vancomycin, and moxifloxacin to help keep endophthalmitis at bay.
Source: Steve Arshinoff, MD

Practitioners are always on the lookout for the most effective agents to keep endophthalmitis at bay following cataract surgery. Investigators led by Steve Arshinoff, MD, associate professor, Department of Ophthalmology and Vision Sciences, University of Toronto, Canada, considered the staying power of three of the most commonly used agents: cefuroxime, vancomycin, and moxifloxacin.
In the study1, investigators developed mathematical models to calculate and compare the abatement rates of these three agents following intracameral administration to determine how long they would be effective. “When you start to look at different antibiotics, you want to know how effective they are because perhaps last week’s data shows that moxifloxacin is the safest drug, but then in another city, you get a bacterium that’s highly resistant to moxifloxacin,” Dr. Arshinoff said. “You want to use something else in the region of the resistant strain, but how do you know what to use?”

Weighing abatement profiles

By calculating abatement profiles on the relative duration of efficacy of the three agents, investigators were able to generate graphs and determine the best drug to use. In the case of new agents, investigators thought that it would be important to know how long they last in the eye, how much the patient actually gets, what the concentration is, and how the drug abates. With abatement profiles, it is possible to compare the agents and determine what you’re getting with each, Dr. Arshinoff noted.
One issue with such profiles, however, is the need to generate constants of anterior chamber abatement since taking hourly objective measures is not feasible. Dr. Arshinoff said that in a study2 on intracameral moxifloxacin, he and fellow investigators mentioned that the numbers would be prone to being updated as they got better data for various rates.
In the recent study, investigators refined the numbers slightly and expanded on the framework. With more data collected for the drugs for the past 2 years, they decided to see what happened when they compared cefuroxime, vancomycin, and moxifloxacin rather than just concentrating on intracameral moxifloxacin alone. “Now that we have all three of them, we can compare them and look at their different lines of resistance,” Dr. Arshinoff said.
Of the three drugs, investigators found that moxifloxacin had the most to offer for endophthalmitis prophylaxis. “Moxifloxacin is the most effective drug with the biggest gap between the dose you have in the eye and the resistance levels of the targeted bacteria,” Dr. Arshinoff said. If you look at how long this lasts in the eye, you can expect that the moxifloxacin should be efficacious for about 40 hours after injection, under ideal circumstances. “But the other drugs, vancomycin and cefuroxime, at best last half as long,” he said.
When using the moxifloxacin intracamerally, Dr. Arshinoff finds that it’s best to dilute it because this has a lower risk of toxicity. Even after using the agent in more than 9,000 cases, he has not seen any adverse effects with the moxifloxacin. Without intracameral antibiotics, many surgeons report seeing a low incidence of cases of anterior chamber fibrin on postop day 1, something he views as probably reflective of low-grade infection. Dr. Arshinoff said he has not seen a single such case among all 9,000 intracameral moxifloxacin patients. “The eyes are typically crystal clear the next day,” he said.

BAIT syndrome concerns

A new case report3 published in JCRS Online Case Reports pointed at one potential concern with intracameral moxifloxacin, a condition known as BAIT (bilateral acute iris transillumination) syndrome. In this case report, investigators described what happened to a patient who underwent vitrectomy for floaters. In one eye, the patient wasn’t given any intracameral antibiotic prophylaxis and had no complications. “In the second eye, they gave the patient intracameral moxifloxacin in the anterior chamber, not in the vitreous, and the patient got unilateral BAIT-type syndrome,” he said.
Another study may also have implications here. Dr. Arshinoff cited an investigation4 on those receiving moxifloxacin and other fluoroquinolone users to see if there was an increased risk of inflammation or an inflammatory disorder. “Investigators wanted to see if the patients who received the moxifloxacin and got BAIT syndrome had underlying systemic disease that predisposed them to iritis,” Dr. Arshinoff said, adding that investigators found that all of the patients had a predisposing disorder such as ankylosing spondylitis. Because the patients presented with the bilateral iritis after getting the moxifloxacin, the authors theorized that perhaps moxifloxacin was acting as a trigger in patients predisposed to iritis.
Oral administration of moxifloxacin achieves a much higher vitreous concentration of the drug than postoperative intracameral administration. The initial anterior chamber concentration of moxifloxacin after intracameral administration is, however, as high as the orally achieved vitreous levels, but quickly abates. It is possible that after administering the intracameral dose in a phakic eye that the high intracameral moxifloxacin dose became trapped behind the iris, in front of the human lens, and thereby triggered the BAIT-like syndrome. This has never been seen with operative administration of intracameral moxifloxacin after cataract surgery, where the IOL is not in contact with the iris, and the intracameral moxifloxacin rapidly abates from the initial injected level, Dr. Arshinoff said.
Nick Mamalis, MD, professor of ophthalmology, Moran Eye Center, University of Utah, Salt Lake City, pointed out that what made this recent case unique was that the BAIT-like syndrome was unilateral with intracameral moxifloxacin given. “The previous cases of whatever causes this BAIT-like syndrome were associated with bilateral disease,” Dr. Mamalis said. Also, while it has been associated with systemic moxifloxacin, in only one investigation were some of the cases associated with intraocular moxifloxacin.
He noted that the case involved a vitrectomy, not cataract surgery. “Usually when you have to do a vitrectomy, you give intravitreal antibiotics, but they gave intracameral moxifloxacin,” Dr. Mamalis said. “The patient was fine initially in the postoperative period and developed this condition 3 weeks later.” While it’s always difficult to ascribe a syndrome like this to an intracameral injection after a prolonged period, such delays have been seen in other syndromes, Dr. Mamalis noted. For example, with hemorrhagic occlusive retinal vasculitis (HORV) there is a delayed onset of the severe inflammatory reaction, which may not occur until a couple of weeks after surgery. “The fact that it’s delayed doesn’t mean that you can’t ascribe it to the moxifloxacin, but there’s no proof,” he said. “It’s hard to ascribe any significance to a one-time occurrence when we’re still not sure that the antibiotic is the cause.”
On the other hand, you can’t dismiss something because there has been a large amount of an agent used without an issue, Dr. Mamalis stressed, adding that with HORV, there were those who proclaimed that vancomycin had been used for 20,000 cases and this had never been seen.
Overall, when it comes to keeping endophthalmitis at bay, Dr. Mamalis thinks that moxifloxacin has been shown to be a valuable medication. The intracameral dosing of the preservative-free moxifloxacin in multiple studies has not been shown to cause any form of toxicity and certainly nothing like this BAIT syndrome, he stressed. “With just one case, we still don’t know for sure if it’s related to the antibiotic, but I would not recommend that surgeons consider stopping moxifloxacin,” Dr. Mamalis said. “I think it’s a valuable antibiotic to use, and I think study after study has shown that it’s safe in the small dose that we use in the anterior chamber following surgery.”